Regulation of pancreatic protein synthesis by cholecystokinin and calcium.
The effect of cholecystokinin (CCK) on [3H]phenylalanine and [14C]tyrosine incorporation into protein was studied in isolated rat pancreatic acini. CCK8, the biologically active octapeptide of CCK, had a biphasic effect on amino acid incorporation. The magnitude of the stimulatory effect (maximal at 10(-10) to 3 X 10(-10) M CCK8) was greater in diabetic rats, whereas the magnitude of the inhibitory effect (maximal at 10(-8) M CCK8) was greater in normal rats. Omission of extracellular Ca2+ from the incubation media did not diminish the stimulatory action of CCK8. Addition of 10(-4) M EGTA to media containing no added Ca2+ lowered basal incorporation, abolished CCK's stimulatory effect and enhanced its inhibitory effect. Stimulation was restored in the presence of Ca2+. The stimulatory effect of the cholinergic analogue carbachol (10(-5) M) on amino acid incorporation was also abolished by removal of extracellular Ca2+, whereas the stimulatory effect of insulin (1.67 X 10(-8) M) remained intact. These findings suggest that CCK and other pancreatic secretagogues enhance pancreatic protein synthesis via Ca2+, whereas stimulation by insulin occurs via another mechanism.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D010649:Phenylalanine; D004533:Egtazic Acid; D002766:Cholecystokinin; D002118:Calcium